Novel highly-soluble peptide-chitosan polymers: Chemical synthesis and spectral characterization

Novel water-soluble polymers, N-(gamma-propanoyl-valin)-chitosan and N-(gamma-propanoyi-aspartic acid)-chitosan, were synthesized by reaction of low molecular weight chitosan with N-alpha-(3-bromopropanoyl)-valine and N-alpha-(3-bromopropanoyl)-aspartic acid, respectively, under mild conditions. Prior to reaction with chitosan, the peptide substituents have been prepared by standard peptide chemistry methods from 3-bromopropanoic acid and the relevant a-amino acid tert-butyl esters. The chemical structure and physical properties of the novel chitosan derivatives were characterized by H-1 NMR and IR spectroscopy. The polymers are highly soluble in a wide pH range, which opens new perspectives for the applications of chitosan-based materials

Radiochemical and biological evaluation of novel Sm-153/Ho-166-amino acid-chitosan complexes

Sm-153/Ho-166-chitosan complexes have been considered promising agents for internal radiation therapy. By direct administration, complexes solution converts into a gel, at physiological pH, allowing its retention for a long time. Herein, we report on the synthesis of Sm-153/Ho-166 complexes with the novel amino acid-chitosan polymers, N-(gamma-propanoylvalin)-chitosan (CHICO-val) and N-(gamma-propanoyl-aspartic acid)-chitosan (CHICO-asp). The main goal of this study was to obtain data on the radiochemical and biological behaviour of these complexes and information regarding their therapeutic potential when compared to Sm-153/Ho-166-chitosan. Radiolabelling yield of Sm-153/Ho-166-amino acid-chitosan complexes was dependent on polymer concentration but less dependent on pH. Radiochemical stability was shown to be higher for amino acid-chitosans than for chitosan, with Sm-153/Ho-166-CHICO-val being stable up to 3 h, while Sm-153/Ho-166-CHICO-asp is stable up to 24 h. In the presence of ascorbic acid radiochemical stability of Sm-153/Ho-166-CHICO-val and Sm-153/Ho-166-CHICO was improved, decreasing for Sm-153/Ho-166-CHICO-asp. In vivo behaviour of Sm-153 complexes was studied in mice. The radioactive amino acid-chitosans can be directly injected into blood stream without significant retention on injection site, being trapped by liver. Biodistribution studies suggest that the radioactive amino acid-chitosans, due to its water solubility and stability may be considered potential candidates to be further explored for liver targeted nuclear therapy

A discrete geometric model of concurrent program execution

A trace of the execution of a concurrent object-oriented program can be displayed in two-dimensions as a diagram of a non-metric finite geometry. The actions of a programs are represented by points, its objects and threads by vertical lines, its transactions by horizontal lines, its communications and resource sharing by sloping arrows, and its partial traces by rectangular figures. We prove informally that the geometry satisfies the laws of Concurrent Kleene Algebra (CKA); these describe and justify the interleaved implementation of multithreaded programs on computer systems with a lesser number of concurrent processors. More familiar forms of semantics (e.g., verification-oriented and operational) can be derived from CKA. Programs are represented as sets of all their possible traces of execution, and non-determinism is introduced as union of these sets. The geometry is extended to multiple levels of abstraction and granularity; a method call at a higher level can be modelled by a specification of the method body, which is implemented at a lower level. The final section describes how the axioms and definitions of the geometry have been encoded in the interactive proof tool Isabelle, and reports on progress towards automatic checking of the proofs in the paper

Automated Algebraic Reasoning for Collections and Local Variables with Lenses

Lenses are a useful algebraic structure for giving a unifying semantics to program variables in a variety of store models. They support efficient automated proof in the Isabelle/UTP verification framework. In this paper, we expand our lens library with (1) dynamic lenses, that support mutable indexed collections, such as arrays, and (2) symmetric lenses, that allow partitioning of a state space into disjoint local and global regions to support variable scopes. From this basis, we provide an enriched program model in Isabelle/UTP for collection variables and variable blocks. For the latter, we adopt an approach first used by Back and von Wright, and derive weakest precondition and Hoare calculi. We demonstrate several examples, including verification of insertion sor

Subgingival Microbiome Colonization and Cytokine Production during Early Dental Implant Healing

Little is known about longitudinal development of the peri-implant subgingival microbiome and cytokine production as a new sulcus forms after dental implant placement. Therefore, the purpose of this observational study was to evaluate simultaneous longitudinal changes in the oral microbiome and cytokine production in the developing peri-implant sulcus compared to control natural teeth. Four and 12 weeks after implant placement and abutment connection, a dental implant and a natural tooth were sampled in 25 patients for subgingival plaque and gingival crevicular fluid (GCF [around teeth] and peri-implant crevicular fluid [PICF] around implants). DNA from plaque samples was extracted and sequenced using Illumina-based 16S rRNA sequencing. GCF and PICF samples were analyzed using a customized Milliplex human cytokine and chemokine magnetic bead panel. Beta diversity analysis revealed that natural teeth and implants had similar subgingival microbiomes, while teeth had greater alpha diversity than implants. At the genus level, however, few differences were noted between teeth and dental implants over 12 weeks. Specifically, Actinomyces and Selenomonas were significantly elevated around teeth versus dental implants at both 4 weeks and 12 weeks, while Corynebacterium and Campylobacter were significantly elevated only at 4 weeks around teeth. The only difference between PICF and GCF biomarkers was significantly elevated granulocyte-macrophage colony-stimulating factor levels around teeth versus dental implants at the 4-week visit. The subgingival microbiome and cytokine production were similar between teeth and implants during early healing, suggesting that these profiles are driven by the patient following dental implant placement and are not determined by anatomical niche

Ab-initio study of model guanine assemblies: The role of pi-pi coupling and band transport

Several assemblies of guanine molecules are investigated by means of first-principle calculations. Such structures include stacked and hydrogen-bonded dimers, as well as vertical columns and planar ribbons, respectively, obtained by periodically replicating the dimers. Our results are in good agreement with experimental data for isolated molecules, isolated dimers, and periodic ribbons. For stacked dimers and columns, the stability is affected by the relative charge distribution of the pi orbitals in adjacent guanine molecules. pi-pi coupling in some stacked columns induces dispersive energy bands, while no dispersion is identified in the planar ribbons along the connections of hydrogen bonds. The implications for different materials comprised of guanine aggregates are discussed. The bandstructure of dispersive configurations may justify a contribution of band transport (Bloch type) in the conduction mechanism of deoxyguanosine fibres, while in DNA-like configurations band transport should be negligible.Comment: 21 pages, 6 figures, 3 tables, to be published in Phys. Rev.

Composition Dependence of the Structure and Electronic Properties of Liquid Ga-Se Alloys Studied by Ab Initio Molecular Dynamics Simulation

Ab initio molecular dynamics simulation is used to study the structure and electronic properties of the liquid Ga-Se system at the three compositions Ga$_2$Se, GaSe and Ga$_2$Se$_3$, and of the GaSe and Ga$_2$Se$_3$ crystals. The calculated equilibrium structure of GaSe crystal agrees well with available experimental data. The neutron-weighted liquid structure factors calculated from the simulations are in reasonable agreement with recent neutron diffraction measurements. Simulation results for the partial radial distribution functions show that the liquid structure is closely related to that of the crystals. A close similarity between solid and liquid is also found for the electronic density of states and charge density. The calculated electronic conductivity decreases strongly with increasing Se content, in accord with experimental measurements.Comment: REVTeX, 8 pages and 12 uuencoded PostScript figures, submitted to Phys. Rev. B. corresponding author: [email protected]

Calculational Verification of Reactive Programs with Reactive Relations and Kleene Algebra

Reactive programs are ubiquitous in modern applications, and so verification is highly desirable. We present a verification strategy for reactive programs with a large or infinite state space utilising algebraic laws for reactive relations. We define novel operators to characterise interactions and state updates, and an associated equational theory. With this we can calculate a reactive program’s denotational semantics, and thereby facilitate automated proof. Of note is our reasoning support for iterative programs with reactive invariants, which is supported by Kleene algebra. We illustrate our strategy by verifying a reactive buffer. Our laws and strategy are mechanised in Isabelle/UTP, which provides soundness guarantees, and practical verification support